Presentation and treatment of two cases of malignant struma ovarii.

BACKGROUND: Malignant Struma Ovarii (MSO) is a rare type of germ cell tumour which is diagnosed postoperatively on surgical pathology specimens by the presence of differentiated thyroid cancer in mature cystic teratomas in the ovaries. Treatment and follow-up procedures are not clearly established due to the paucity of MSO cases. CASE 1: A 44-year-old multiparous female presented with an irregular period. Ultrasound showed a left ovarian lesion mostly a dermoid cyst, however, CT showed a 3.8 × 2.7 × 4 cm complex cystic lesion with thick septation and enhancing soft tissue component. Laparoscopic left salpingo-oophorectomy was performed and histopathology showed a follicular variant of papillary thyroid carcinoma arising in a mature cystic teratoma. Peritoneal cytology was positive for malignancy. A thyroid function test was normal before surgery. Total thyroidectomy was performed followed by radioactive (RAI) iodine therapy. Later, a total laparoscopic hysterectomy and right salpingo-oophorectomy were performed. There is no evidence of recurrent disease during the 26-months follow-up. CASE 2: A 46-year-old single female presented with left lower abdominal pain that had persisted for 2 months. Imaging revealed an 8 × 9 × 9.5 cm left ovarian mass. Laparoscopic left salpingo-oophorectomy was performed and histopathology showed mature cystic teratoma with small papillary thyroid cancer. CT showed no evidence of metastatic disease. Later, the patient had a total thyroidectomy followed by radioactive (RAI) iodine therapy. She was started on thyroxine and later had total abdominal hysterectomy and right salpingo-oophorectomy. CONCLUSION: MSO is a very rare tumour. Preoperative diagnosis is very difficult because of the nonspecific symptoms and the lack of specific features in imaging studies. Also, there is no consensus on the optimal treatment of women with MSO. Our two cases add to the limited number of MSO cases.

Identification of Germline FOXE1 and Somatic MAPK Pathway Gene Alterations in Patients with Malignant Struma Ovarii, Cleft Palate and Thyroid Cancer.

Germline variants in the FOXE1 transcription factor have been associated with thyroid ectopy, cleft palate (CP) and thyroid cancer (TC). Here, we aimed to clarify the role of FOXE1 in Portuguese families (F1 and F2) with members diagnosed with malignant struma ovarii (MSO), an ovarian teratoma with ectopic malignant thyroid tissue, papillary TC (PTC) and CP. Two rare germline heterozygous variants in the FOXE1 promoter were identified: F1) c.-522G>C, in the proband (MSO) and her mother (asymptomatic); F2) c.9C>T, in the proband (PTC), her sister and her mother (CP). Functional studies using rat normal thyroid (PCCL3) and human PTC (TPC-1) cells revealed that c.9C>T decreased FOXE1 promoter transcriptional activity in both cell models, while c.-522G>C led to opposing activities in the two models, when compared to the wild type. Immunohistochemistry and RT-qPCR analyses of patients' thyroid tumours revealed lower FOXE1 expression compared to adjacent normal and hyperplastic thyroid tissues. The patient with MSO also harboured a novel germline AXIN1 variant, presenting a loss of heterozygosity in its benign and malignant teratoma tissues and observable ß-catenin cytoplasmic accumulation. The sequencing of the F1 (MSO) and F2 (PTC) probands' tumours unveiled somatic BRAF and HRAS variants, respectively. Germline FOXE1 and AXIN1 variants might have a role in thyroid ectopy and cleft palate, which, together with MAPK pathway activation, may contribute to tumours' malignant transformation.

Struma Ovarii With Extensive Peritoneal Implants Metastasis Revealed by 99m TcO 4 SPECT/CT.

ABSTRACT: Struma ovarii is a rare form of ovarian teratoma composed entirely or mainly of mature thyroid tissue. A 55-year-old woman with persistent hypogastric pain for 4 months was admitted to our hospital. She had undergone resection of struma ovarii 4 years ago. Contrast-enhanced CT shows multiple significantly enhanced nodules scattered in the abdominopelvic cavity. Pathological examination of the nodule in the left pararenal region demonstrated thyroid-like follicular epithelium. Herein, we present the 99m TcO 4 whole-body scintigraphy SPECT/CT findings of a case of struma ovarii with extensive peritoneal implants metastasis. Then, she was treated with total thyroidectomy and 131 I therapy.

Role of gene sequencing in classifying struma ovarii: BRAF p.G469A mutation and TERT promoter alterations favour malignant struma ovarii.

AIMS: Struma ovarii (SO) are rare, accounting for 0.3-1% of ovarian tumours, and include benign and malignant lesions. In most cases, histology is not predictive of clinical outcome and prognosis. The prognosis of histologically malignant thyroid-type carcinomas can indeed be excellent, while SO, composed of normal thyroid tissue, can recur and are designated highly differentiated follicular carcinoma of the ovary. Clearer diagnostic criteria are therefore required. METHODS AND RESULTS: We retrospectively studied 31 SO using DNA and RNA sequencing with pan-cancer gene panels, including eight biologically malignant SO (BMSO) defined based on ovarian serosal or extra-ovarian dissemination at presentation or during follow-up, 10 stage IA histologically malignant SO (HMSO) with thyroid-type carcinoma morphology and 13 biologically and histologically benign SO (BSO), with none of the above-mentioned characteristics. Molecular alterations were observed in 87.5% of BMSO, 70% of HMSO and 7.7% of BSO (P < 0.001). All patients with a peritoneal dissemination at presentation or during follow-up had at least one gene alteration. BRAF mutations (44.5%) were only observed in malignant forms (HMSO and BMSO) and TERT promoter alterations (25%) only in cases of BMSO. The BRAF p.G469A mutation, which is extremely rare in thyroid carcinomas, was the molecular alteration most frequently associated with malignant SO (28.5%). CONCLUSION: Our results highlight the clinical utility of molecular sequencing in SO, based on this limited number of cases. However, as malignant SO evolve slowly, more extensive molecular studies in SO with more than 10 years' follow-up are required to draw any conclusions on the prognostic value of the associated gene alterations.

Neoplasms in Struma Ovarii: A Review.

Struma ovarii is a well-known ovarian teratoma made up of benign thyroid tissue. These lesions demonstrate variable, normal architecture and normal thyroid immunohistochemical staining with positivity for TTF1, PAX8, and thyroglobulin. Though most are benign, some of these lesions can also present with a malignant component. Within this article, we review the most common diagnostic malignancies including papillary thyroid carcinoma, strumal carcinoid, highly differentiated follicular thyroid carcinoma, and other thyroid carcinomas. We additionally review the use of TTF1 staining to assist in differentiating these lesions from surrounding gynecologic epithelium, which is imperative in making such diagnoses. In highlighting these entities, we hope to provide practicing pathologists with an effective and concise review of these lesions to assist in more challenging cases of struma ovarii.

Incidence, clinical characteristics, and survival outcomes of ovarian strumal diseases: a retrospective cohort study.

BACKGROUND: Struma ovarii (SO) is a rare tumor and may transform into ovarian strumal carcinoid (OSC) and/or malignant struma ovarii (MSO), but the incidence, clinical characteristics, and survival outcomes have not been well defined. METHODS: We conducted a retrospective study of patients with ovarian strumal diseases treated in the our hospital between 1980 and 2022. Subgroup analyses of SO, OSC, and MSO were subsequently performed. RESULTS: A total of 275 cases (2.14%) were identified in a cohort of 12,864 patients with ovarian teratomas, where SO, OSC, and MSO accounted for 83.3%, 12.0%, and 4.7% of cases, respectively. There were no significant differences in age, tumor sizes, elevated tumor markers, and ascites among the three subgroups. At initial treatment, all patients with SO or OSC had FIGO stage I disease except one SO patient presenting metastatic disease, ten patients had MSO confined to the ovary, whereas other three patients had metastatic diseases. Two patients with SO respectively relapsed at peritoneum and anterior mesorectum, while none of the OSC patients presented tumor recurrence or death despite different surgical procedures employed. The 5-year recurrence-free survival rate was 88.9%, and only one death occurred at 9.5 years after diagnosis in patients with MSO. Radioiodine therapy showed satisfactory therapeutic efficacy, but these patients showed poor responses to the chemotherapy. CONCLUSION: 2.14% of ovarian teratoma could be classified as SO, of which 12.0% and 4.7% of SO may transform into OSC and MSO, repsectively. The survival outcomes were excellent even after SO transformed into OSC or MSO. SYNOPSIS: SO occupied 2.14% of ovarian teratoma, where 12.0% and 4.7% of SO may transform into OSC and MSO, respectively, and had excellent survival outcomes.

Struma ovarii with synchronous ascites and elevated CA125 level: a retrospective cohort study.

BACKGROUND: Benign struma ovarii (SO) with synchronous ascites and elevated CA125 level is extremely rare that the incidence, clinical characteristics, and risk factors remain unclear. METHODS: We conducted a retrospective study of patients with SO treated in our hospital between 1980 and 2022. Logistic regression was used to identify potential risk factors for SO patients presenting with ascites and elevated CA125 levels. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the identified risk factors. RESULTS: A total of 21 patients with synchronous ascites and elevated CA125 levels were identified in 229 patients with SO, the crude incidence rate was 9.17%, and four patients (1.75%) had pseudo-Meigs' syndrome. Ascites were completely involuted within 1 month postoperatively and the serum CA125 level decreased to normal between 3 d and 6 weeks after surgery. Multivariate logistic regression showed that age ≥49 years (OR 3.71, 95% CI 1.29 - 10.64, p = 0.015), tumor size ≥10.0 cm (OR 8.79, 95% CI 3.05 - 25.35, p < 0.001), and proliferative SO (OR 11.16, 95% CI 3.01 - 41.47, p < 0.001) were the independent risk factors for patients presenting ascites and elevated CA 125 level. The ROC curve revealed that the predictive performance for age and tumor size was unsatisfactory with an area under the curve (AUC) was 0.646 and 0.682, respectively. Linear regression demonstrated that the serum CA125 level has a moderate positive correlation with the volume of ascites (log2CA125 = 0.6272*log2ascites + 2.099, p = 0.0001, R2 = 0.5576). CONCLUSIONS: Less than one-tenth of patients with SO would present ascites and elevated CA125 levels, while age ≥49 years, tumor sizes ≥10 cm, and the presence of proliferative SO were the risk factors.

Mature cystic teratoma of the ovary with malignant transformation of tall cell subtype of papillary thyroid carcinoma.

Malignancies rarely occur in somatic parts of mature cystic teratoma of the ovary. Squamous cell carcinoma is the most common form of cancer that can develop in mature cystic teratoma. Other less frequent malignancies include melanoma, sarcoma, carcinoid, and germ cell neoplasms. Only three cases have been reported as papillary thyroid carcinoma arising in struma ovarii. We present a unique case of a 31-year-old female patient who presented with a left ovarian cyst and underwent conservative surgical management in the form of cystectomy. Histopathological examination confirmed the diagnosis of a tall cell subtype of papillary thyroid carcinoma arising from a small focus of thyroid tissue in a mature cystic teratoma of the ovary. The patient was followed up for 60 months with an uneventful clinical course. For a better understanding of such rare cancers, collaborative retrospective studies on large databases with other medical centers are required.

Synchronous thyroid cancer and malignant struma ovarii: concordant mutations and microRNA profile, discordant loss of heterozygosity loci.

BACKGROUND: Struma ovarii is an unusual ovarian teratoma containing predominantly thyroid tissue. Less than 10% of cases undergo malignant transformation in the thyroid tissue and are considered malignant struma ovarii (MSO). MSO have been reported with concurrent thyroid lesions, but molecular data is lacking. CASE PRESENTATION: A 42-year-old female developed MSO and synchronous multifocal subcentimeter papillary thyroid carcinoma (PTC). The patient underwent a salpingo-oophrectomy, thyroidectomy, and low-dose radioactive iodine ablation. Both the thyroid subcentimeter PTC and MSO were positive for BRAF V600E mutation, and microRNA expression profiles were similar across all tumor deposits. However, only the malignant component demonstrated extensive loss of heterozygosity (LOH) involving multiple tumor suppressor gene (TSG) chromosomal loci. CONCLUSIONS: We present the first reported case of MSO with synchronous multifocal subcentimeter PTC in the thyroid containing concordant BRAF V600E mutations and resulting with discordant LOH findings. This data suggests that loss of expression in tumor suppressor gene(s) may be an important contributor to phenotypic expression of malignancy.

Clinical characteristics and survival outcomes in patients with primary ovarian carcinoid: A historical cohort study.

INTRODUCTION: Primary ovarian carcinoids are extremely rare ovarian tumors, and there is limited data available on their clinical characteristics and survival outcomes. MATERIAL AND METHODS: We conducted a historical cohort study of 56 patients to investigate their clinical characteristics. The overall survival, disease-specific survival, recurrence-free survival, and potential prognostic factors of these patients were also evaluated. RESULTS: The median age of these patients was 42.0 years (range: 20-71). The average mass and carcinoid size was 7.3 and 0.4 cm, respectively. Elevated tumor marker levels and ascites were observed in 15 and 10 patients, respectively. In 98.2% of the patients, tumors were confined to the ovary, while only one had metastatic disease. Surgery was the mainstay therapy: 37.5% of the patients underwent unilateral salpingo-oophorectomy, 25.0% underwent hysterectomy with bilateral salpingo-oophorectomy, 21.4% underwent ovarian cystectomy, 10.7% underwent comprehensive staging surgery, and 5.4% underwent bilateral salpingo-oophorectomy. Appendectomy and lymphadenectomy were performed in eight and five patients, respectively, but none showed tumor involvement. Chemotherapy was the only adjuvant treatment utilized, and was administered in four patients. Pathological analysis showed that strumal carcinoid was the most predominant subtype, occurring in 66.1% of the patients. The Ki-67 index was reported in 39 patients, 30 of which had an index of no more than 3%, with a maximum of only 5%. Only one relapse occurred after the initial treatment, and that patient experienced recurrences on two occasions, maintaining stable disease after surgery and octreotide therapy. After a median follow-up of 3.6 years, 96.4% of the patients achieved no evidence of disease, while 3.6% were alive with the disease. The 5-year recurrence-free survival rate was 97.9% and no death occurred. No risk factors for recurrence-free survival, overall survival, or disease-specific survival were identified. CONCLUSIONS: The Ki-67 indices were extremely low and prognoses were excellent in patients with primary ovarian carcinoids. Conservative surgery, especially unilateral salpingo-oophorectomy, is preferred. Individualized adjuvant therapy may be considered for patients with metastatic diseases.

Ovarian strumal carcinoid: a case report.

BACKGROUND: Carcinoid tumors of the ovary are rare tumors, histopathologically classified as monodermal teratomas and somatic-type tumors arising from dermoid cysts. Their malignancy varies from borderline to malignant. Carcinoid tumors can occur in young and elderly women, and are sometimes seen in mature teratoma, struma ovarii, or mucinous cystadenoma as a nodule or tumor. Strumal carcinoid and mucinous carcinoid present as special types of carcinoid tumors of the ovary. CASE REPORT: This report describes a 56-year-old woman who presented with a large pelvic mass on abdominal ultrasonography during a medical examination. The diameter of the pelvic tumor was approximately 11 cm and was suspected to be ovarian cancer. The values of CA125 and CEA were above their reference intervals on preoperative examination. Abdominal total hysterectomy and bilateral salpingo-oophorectomy were performed. Intraoperative frozen-section histopathology suggested a diagnosis of mucinous adenocarcinoma; therefore, partial omentectomy and pelvic lymphadenectomy were also performed. Permanent-section histopathology led to a final diagnosis of strumal carcinoid of the ovary, stage IA (FIGO 2014). Six years post-operation, the patient had no sign of recurrence.

It Does Exist! Diagnosis and Management of Thyroid Carcinomas Originating in Struma Ovarii.

Thyroid carcinoma originating in struma ovarii comprises a small minority of all cases of struma ovarii. Given the rarity of this diagnosis, literature to guide evaluation and management is limited. The most common carcinoma originating from struma ovarii is papillary thyroid carcinoma. Treatment includes surgery, including a fertility sparing approach if disease is confined to the ovary, with consideration of total thyroidectomy and radioactive iodine ablation for high-risk pathologic features or disease spread beyond the ovary. This review discusses the histopathologic findings, molecular pathology, clinical implications and management, and prognosis of thyroid carcinomas originating in struma ovarii.

Computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography findings for the diagnosis of malignant struma ovarii: A case report.

Malignant struma ovarii (MSO) is an extremely rare disease arising from struma ovarii. Preoperative diagnosis is still challenging due to the lack of criteria for imaging findings. Herein, we report a case of MSO with suggestive imaging findings for a 50-year-old woman who presented with a pelvic tumor. The tumor did not typically show characteristic imaging findings of struma ovarii; however, the findings implied colloids of thyroid tissue within solid components on the magnetic resonance imaging (MRI) and computed tomography. Additionally, the solid components showed hyperintensity on diffusion-weighted image and hypointensity on apparent diffusion coefficient maps. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. Histopathological examination revealed MSO of the right ovary, pT1aNXM0. The distribution of papillary thyroid carcinoma tissue corresponded to restricted diffusion area on MRI. In conclusion, the coexistence of imaging findings suggesting thyroid tissue and restricted diffusion in the solid component on MRI could indicate MSO.

Current state of management of struma ovarii and preoperative imaging features: A retrospective case series study of 18 patients at a single institution.

AIM: Even though 95% of struma ovarii are benign, it is often overtreated because of the difficulty to distinguish it from malignancy. In this study, our aim was to evaluate the current state of the preoperative diagnosis and the selection of the surgical procedure, and to improve preoperative diagnostic accuracy by retrospectively reviewing imaging findings. METHODS: We retrospectively reviewed the clinical course and imaging characteristics of 18 patients who were diagnosed postoperatively with struma ovarii, pathologically, at our institution between 2015 and 2021. RESULTS: The preoperative diagnoses included benign ovarian tumor in eight cases, borderline in four cases, and malignant in six cases. None of the cases were diagnosed as struma ovarii preoperatively. Of the seven patients who had confirmed a desire for future childbearing, four patients were suspected for borderline or malignant tumor preoperatively, and underwent abdominal adnexectomy. In patients without a desire for childbearing, laparoscopic surgery was performed in only 45% of the patients whose preoperative diagnosis was benign. On magnetic resonance imaging (MRI), 54% of the cases showed enhanced solid components, which is characteristic of malignant tumors, but diffusion restriction was observed in only 11%. On computed tomography (CT), 78% of the cases showed a high attenuation lesion reflecting thyroid tissue. CONCLUSIONS: Struma ovarii is difficult to distinguish from malignancy preoperatively, making the choice of surgical approach complicated. A comprehensive evaluation of diffusion-weighted MRI and CT findings may improve the accuracy of preoperative diagnosis of struma ovarii.

Struma ovarii with massive ascites mimicking ovarian carcinoma treated with conservative laparoscopic surgery: a case report.

Struma ovarii is a rare taratoma that accounts for 0.5-1% of all ovarian tumors. It is sometimes difficult to differentiate struma ovarii from ovarian carcinoma. We encountered a case of struma ovarii that was suspected to be malignant due to the accumulation of massive ascites and an elevated CA125 level. It was successfully treated with laparoscopic surgery.A 37-year-old nulliparous woman consulted a local physician with a chief complaint of abdominal distention. Computed tomography (CT) of the abdomen revealed a pelvic tumor with a large amount of ascites. She was referred to our department. Contrast-enhanced magnetic resonance imaging (MRI) and CT showed bilateral ovarian tumors with multicystic and solid components. CA125 level was markedly elevated. Two cytological examinations of ascites showed no malignant cells. Preoperatively, malignancy was strongly suspected, but considering the possibility of a benign ovarian tumor, laparoscopic surgery was scheduled. During laparoscopic surgery, 4,850 mL of ascites were aspirated, and the left adnexa was removed. Intraoperative rapid pathology suggested struma ovarii with no evidence of malignancy. Postoperative pathology showed mature teratoma and struma ovarii.Although struma ovarii is benign in 90-95% of cases, there have been scattered case reports in which suspected malignancy led to unnecessary or excessive surgery. We propose that appropriate preoperative imaging and accurate intraoperative rapid pathology can prevent excessive surgery, conservative or laparoscopic excisions should be considered.

A patient with advanced breast cancer and hyperthyroidism associated with struma ovarii.

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